1. Drugs used to facilitate clotting
    1. Fibrinolytic inhibitors
      1. MOA: competitively inhibits plasminogen activation
        1. Aminocaproic acid
          1. Adverse effects
          2. Intravascular thrombosis
          3. Hypotension
          4. Must give a 30 min loading dose to prevent hypo
    2. Serine protease inhibitors
      1. MOA: inhibits fibrinolysis by free plasmin
        1. Aprotinin
          1. serine protease inhibitor
          2. reduces bleeding from surgery
    3. Clotting factors
      1. Factor VII deficiency
        1. fresh-frozen plasma
        2. prothrombin complex concentrates
        3. recombinant factor VIIa
      2. Hemophilia A
        1. recombinant factor VIII
        2. cryoprecipitate
      3. Hemophilia B/Christmas disease
        1. recombinant factor IX products
      4. Stuart-Prower defect (X)
        1. FFP
        2. prothrombin complex concentrates
      5. Von Willebrand disease
        1. factor VIII concentrates containing VWF
        2. cryoprecipitate
      6. Subtopic 6
    4. Vitamin K
      1. MOA: relieves depression of prothrombin activation
      2. Use
        1. Excessive warfarin administration
        2. Vitamin K deficiency
          1. adults
          2. all neonates
  2. Anticoagulation drugs
    1. Indirect thrombin inhibitors
      1. MOA: Interact with AT III to inhibit thrombin
        1. Heparin
          1. Adverse effects
          2. BLEEDING
          3. HIT: Heparin-induced Thrombocytopenia
          4. Immunogenic, hapten-like response to the factor IV-heparin complex, causing thrombi, thrombocytopenia, and decreased platelet count
          5. Precautions
          6. oral causes hematoma - use IV, SC only
          7. closely monitor: aPTT, protamine concentration, anti-Xa units
          8. short half-life; use other indirects for more convenient administration
          9. preferred for pregnant women
          10. Antidote
          11. STOP THE DRUG
          12. protamine sulfate
      2. MOA: Inhibit Xa
        1. LMWH
          1. Less side effects, no aPTT monitoring
          2. EnoxaPARIN
          3. DaltePARIN
          4. TinzaPARIN
        2. Fondaparinux
          1. Use in case of HIT
    2. Direct thrombin inhibitors
      1. MOA: directly bind the active site of thrombin
        1. bivalent: irreversible inhibitors also bind to the substrate recognition site
          1. Bivalirudin
          2. Hirudin
          3. recombinant form of hirudin
          4. Lepirudin
          5. Good for HIT
          6. Bad in pts with renal insufficiency
      2. Argatroban
        1. Use
          1. USE in HIT
          2. IV, monitor aPTT
        2. Precautions
          1. Liver clearance
      3. Dabigatran
        1. Use
          1. ORAL
          2. fast onset
        2. Precautions
          1. CONTRAINDICATED in renal failure
          2. fatal bleeding
          3. NO ANTIDOTE
    3. Vitamin K antagonist
      1. Warfarin
        1. MOA
          1. Blocks the γ-carboxylation of the glutamate residue in prothrombin, VII, IX, X, protein C & S by inhibiting VITAMIN K EPOXIDE REDUCTASE
        2. Use
          1. ORAL: 5-10 mg standard dose
          2. slow onset/offset: 8-12 hrs
          3. Therapeutic range = INR of 2-3
          4. 1 week for PT to adjust
        3. Adverse reactions
          1. Skin necrosis (WISN) during first week
          2. DVT with decreased protein C activity
        4. Precautions
          1. CONTRAINDICATED in pregnancy (crosses the placenta)
          2. Causes hemorrage, birth defects in the fetus
        5. Antidotes
          1. Excessive anticoagulant effect & bleeding
          2. STOP THE DRUG
          3. Give Vit K1, fresh-frozen plasma, prothrombin complex concentrates, rFVIIa
    4. Factor Xa inhibitor
      1. Rivaroxaban
        1. Use
          1. ORAL
          2. fast onset
        2. Precautions
          1. LIVER METABOLISM/p450 metabolism
          2. Subtopic 2
        3. Antidote
          1. Factor Xa
    5. ORAL ANTICOAGULANTS
      1. Drug interactions - oral anticoagulants
      2. Direct thrombin inhibitor
        1. dabigatran
      3. Vitamin K antagonist
        1. warfarin
      4. Factor Xa Inhibitor
        1. rivaroxaban
  3. Thrombolytic drugs
    1. MOA: binds and activates plasmin
      1. Streptokinase
        1. Hypersensitivity (only use once)
      2. Anistreplase
        1. Complex of human plasminogen + streptokinase
    2. MOA: directly converts plasmin to plasminogen
      1. Urokinase
    3. tissue plasminogen activators (t-PAs)
      1. MOA: preferentially activates fibrin-bound plasminogen
        1. recombinant t-PA
          1. Alteplase
          2. Reteplase
        2. mutant t-PA
          1. Tenecteplase
  4. Antiplatelet Agents
    1. Thromboxane inhibitor
      1. MOA: irreversibly inhibits the synthesis of TXA2
        1. Aspirin
    2. ADP receptor antagonists
      1. MOA: inhibit the platelet's ADP receptor
        1. Clopidogrel
          1. prodrug
          2. slow-onset
          3. Adverse interactions with proton-pump inhibitors (omeprazole)
        2. Ticlopidine
          1. Adverse reactions
          2. Causes TTP
          3. GI toxicity, hemorrage, purpura
    3. IIb/IIIa receptor antagonists
      1. MOA: blocks activation of the IIb/IIIa and vibronectin receptors
        1. Abciximab
      2. MOA: blocks the binding of fibrinogen to the IIb/IIIa receptor only
        1. Eptfibatide
        2. Tirofiban
          1. smaller molecule